|ORIGINAL CONTRIBUTION: NEUROPATHOLOGY
|Year : 2014 | Volume
| Issue : 3 | Page : 186-189
Central nervous system hemangioblastomas: Epidemiology, pathology and clinical spectrum in a tertiary care centre
Sanjay M Chawhan, Aarti A Dani, Saroj A Meshram, Shilpa M Narkhede, Archana A Randale, DK Kumbhalkar
Department of Pathology, Super Speciality Hospital and Government Medical College, Nagpur, Maharashtra, India
|Date of Web Publication||27-May-2015|
Sanjay M Chawhan
Department of Pathology, Super Speciality Hospital and Government Medical College, Nagpur, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Hemangioblastomas are rare, benign, vascular neoplasm. According to the World Health Organization classification of tumors of the nervous system, hemangioblastomas are classified as meningeal tumors of uncertain origin and are Grade I neoplasm. Hemangioblastomas arise either in the setting of von Hippel-Lindau (vHL) disease or more often as solitary sporadic lesions. They account for 1-3% of primary central nervous system (CNS) tumors. The most common location is the cerebellum followed by spinal cord. Supratentorial lesions are rare. Aims: The aim was to study the prevalence of hemangioblastoma. Materials and Methods: A retrospective observational study of 7 years duration was carried out in the department of pathology of a tertiary referral center. The sample received was processed by standard formalin fixing, paraffin embedding method. Serial sections and special stains were studied as and when required. Results: During the period of 7 years, we reported total 679 cases of primary CNS tumors, of which 11 (1.62%) cases were of hemangioblastoma. Ten of them were intracranial, and one was spinal. There were seven male and four female patients that clearly indicate male preponderance. Conclusions: In our study, prevalence of hemangioblastoma was 1.62% (11 cases) out of 679 primary CNS tumors, which is low as per literature. There was a male predominance with male:female ratio 2:1. Cerebellum was the most frequent site (81.8%). No association with vHL disease was noted.
Keywords: Central nervous system tumor, cerebellum, hemangioblastoma, World Health Organization
|How to cite this article:|
Chawhan SM, Dani AA, Meshram SA, Narkhede SM, Randale AA, Kumbhalkar D K. Central nervous system hemangioblastomas: Epidemiology, pathology and clinical spectrum in a tertiary care centre. Astrocyte 2014;1:186-9
|How to cite this URL:|
Chawhan SM, Dani AA, Meshram SA, Narkhede SM, Randale AA, Kumbhalkar D K. Central nervous system hemangioblastomas: Epidemiology, pathology and clinical spectrum in a tertiary care centre. Astrocyte [serial online] 2014 [cited 2020 Sep 27];1:186-9. Available from: http://www.astrocyte.in/text.asp?2014/1/3/186/157762
| Introduction|| |
In 1928, Cushing and Bailey introduced the term hemangioblastoma.  It refers to a benign vascular neoplasm that arises almost exclusively in the central nervous system (CNS). According to the World Health Organization classification of tumors of the nervous system, hemangioblastomas are classified as meningeal tumors of uncertain origin , and are considered as Grade I neoplasm. Hemangioblastoma arises either in the setting of von Hippel-Lindau (vHL) disease or more often as solitary sporadic lesion without extracerebellar stigmata or family history. , According to various series, hemangioblastomas are rare and account for approximately 1-3% of primary CNS tumors. ,, The most common location is cerebellum followed by spinal cord , and medulla.  The occurrence of this tumor in other locations such as supratentorial compartment, ,, optic nerve, , sella turcica,  ventricular system, , peripheral nerves  or soft tissues of extremities  are extremely rare. The clinical presentation of hemangioblastoma usually depends on the anatomical location and growth patterns. In general, intracranial hemangioblastoma present with a long history of minor neurological symptoms that are followed by a sudden exacerbation. Cerebellar lesions may present with ataxia and discoordination or increased intracranial pressure. Patient with spinal cord lesion most frequently presents with pain, followed by signs of spinal cord compression.
| Materials and Methods|| |
This was a 9 retrospective observational study of 7 years duration carried out in the Department of Pathology of a tertiary referral center. During this period, we reported total 679 cases of CNS tumors, of which 11 (1.62%) cases were of hemangioblastoma. The complete clinical and radiological details, in particular cases were noted, whenever available. The sample received was processed by standard formalin fixing, paraffin embedding method. Serial sections and special stains were studied as and when required. In all cases, diagnosis was made by routine histopathological examination with the help of special stains as and when required. Of 11, routine crush smear cytology was done in cases only.
| Observations|| |
Totally, 11 cases of hemangioblastoma were diagnosed during a period of 7 years, from January 2005 to December 2011 at a tertiary care center. During this period, we found 679 cases of CNS tumor out of which 11 (1.62%) cases were of hemangioblastoma. Of 679 cases of CNS tumors, 600 were intracranial, and 79 were spinal tumors. There were 10 (91%) intracranial and 1 (9%) spinal hemangioblastoma. Age of the patients varies from 25 to 72 years [Table 1]. There were seven male and four female patients, which clearly indicate male preponderance [Table 1]. Of 10 intracranial tumors, the lesion was located in the cerebellum in 9 cases (82%) and in 1 case (9%) it was located in the brain stem. The single case of spinal hemangioblastoma was located at thoracic level (9%).
|Table 1: Age-, Sex- and Site-wise Distribution of Hemangioblastoma Cases |
Click here to view
Radiologically, they presented as a contrast enhancing cystic lesions with a mural nodule in nine cases and two cases as heterogeneously cystic lesions. Grossly, size varies from 1 × 1 × 1 cm to 4 × 5 × 2 cm. They were soft in consistency with reddish brown to yellow cut surface. Microscopically, all cases showed anastomosing network of delicate vascular channels supplied by feeding vessel. Stromal cells present in nests or lobule packed between capillary channels were seen in nine cases but in two cases, there were paucity of stromal cells. Stromal cells were large polygonal with vacuolated or foamy cytoplasm with uniform round nuclei. At places, stromal cells showed large, pleomorphic, hyperchromatic nuclei, and smudging of nuclear chromatin but no mitotic activity. Mast cells infiltration was seen in four cases.
| Discussion|| |
Incidence of hemangioblastoma in our series was 1.62%, which corresponds to the incidence observed in the literature. ,, The most common location in our series was cerebellum in nine (82%) cases followed by spinal cord in one (9%) case. , All cases were adults with age ranging from 25 to 72 year in our series. ,,, There was no association of vHL disease in our cases. , In our series, strikingly male preponderance was found. But in the literature, there are studies that showed equal risk in male and female  or moderate male preponderance. ,,
Microscopically, it shows anastomosing network of delicate vascular channels supplied by feeding vessel of larger caliber , [Figure 1] responsible for the name of this entity and its classification as a primary vascular tumor. Actually, neoplastic element of hemangioblastoma is stromal cell.  Stromal cells lie packed between abundant often crisscrossing capillary channels. Cellularity and distribution of stromal cells and its lipid content vary considerably. ,, Stromal cells are large polygonal cells with variable lipid and/or glycogen rich cytoplasm, which give them vacuolated or foamy appearance ,,,, [Figure 2] and [Figure 3]. When stromal cells are present in nests or lobules, it is known as cellular hemangioblastoma, whereas their paucity results in reticular variant. ,, In our series, nine cases were of cellular and two cases were of reticular variant of hemangioblastoma. In seven cases, stromal cells at places showed large, pleomorphic, hyperchromatic nuclei, and smudging of nuclear chromatin ,, [Figure 4]. Four cases showed mast cells infiltration distributed uniformly throughout the tumor  and readily demonstrated with toluidine blue staining. Tumor-brain interface showed a florid piloid astrogliosis and rosenthal fibers in one case.  Foci of extramedullary normopoiesis were not encountered. 
Cellular variant can be confused with secondary deposits of clear cell carcinoma of the kidney. , Secondary deposits of renal cell carcinoma will have an epithelial characteristic. Cells are geometrically arrayed or uniformly aligned relative to vasculature and mitoses will be frequent. ,, Clear cell appearances of renal cell carcinoma cells are due to both glycogen and lipid content.  Although hemangioblastoma is lipid-rich, they may contain a considerable amount of glycogen. ,,,, Thus, preclude their distinction from renal cell carcinoma on the basis of simple periodic acid-Schiff and diastase preparation alone.  On immunohistochemistry (IHC) staining, stromal cells fail to express epithelial membrane antigen (EMA), distinguishing the hemangioblastoma from metastatic renal cell carcinoma. , Cytoplasmic labeling for inhibin alpha further distinguishes the hemangioblastoma from clear cell carcinoma of renal origin. 
Cellular variant can be confused with lipidized angiomatous meningioma. Angiomatous meningioma will have thick-walled hyalinized vessels and will show sheets of meningiothelial cells at places.  On IHC staining; stromal cells fail to express EMA distinguishing the hemangioblastoma from lipidized angiomatous meningioma. 
Reticular variant can be confused with angiomas. In angiomas, vessels are closely opposed leaving little if any interstitial parenchyma, but reticular variant will show few stromal cells at places. ,, Stromal cells often label for S100 protein and neural specific enolase, facilitate the distinction of hemangioblastoma from hemangiopericytoma and angiomas. 
Surgical excision is the treatment of choice. Radiotherapy is recommended for nonresectable or recurrent tumor.  A solid gross configuration and paucity of stromal cells may be correlated with symptomatic tumor regrowth.  Underlying vHL disease carries special risk of multifocal hemangioblastomas with an increased incidence of extracerebellar primaries. ,, Cerebrospinal fluid dissemination rarely recorded years after successful resection of cerebellar hemangioblastoma. 
| References|| |
Cushing H, Bailey P. Tumors Arising from Blood Vessels of the Brain: Angiomatous Malformations and Hemangioblastomas. Springfield, Ill: Charles C Thomas Publisher; 1928.
Rubinstein LJ. Atlas of Tumor Pathology: Tumors of the Central Nervous System. Washington, DC: US Government Printing Office; 1972. p. 235.
Gonzales MF. Classification and pathogenesis of brain tumors. In: Kaye AH, Laws ER, editors. Brain Tumors. 1 st
ed. New York: Churchill Livingstone; 1995. p. 31-45.
Neumann HP, Eggert HR, Weigel K, Friedburg H, Wiestler OD, Schollmeyer P. Hemangioblastomas of the central nervous system. A 10-year study with special reference to von Hippel-Lindau syndrome. J Neurosurg 1989;70:24-30.
Conway JE, Chou D, Clatterbuck RE, Brem H, Long DM, Rigamonti D. Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurgery 2001;48:55-62.
Tarantino R, Isidori A, Raco A, Missori P. Supratentorial hemangioblastoma in a patient with breast cancer. A case report. J Neurosurg Sci 2000;44:137-9.
Iplikçioglu AC, Yaradanakul V, Trakya U. Supratentorial haemangioblastoma : A ppearances on MR imaging. Br J Neurosurg 1997;11:576-8.
Berger PC, Scheithauer BW. Tumors of the central nervous system. Atlas of Tumor Pathology. Series 3, Fascicle 10. Tumors of Uncertain Origin. Ch. 7. Washington DC: Armed Forces Institute of Pathology; 1994. p. 239-43.
Boughey AM, Fletcher NA, Harding AE. Central nervous system haemangioblastoma : A clinical and genetic study of 52 cases. J Neurol Neurosurg Psychiatry 1990;53:644-8.
Bohling T, Plate KH, Haltia MJ, Alitalo K, Neumann HP. Von Hippel Lindau disease and capillary hemangioblastoma. In: Kleihues P, Cavenee WK, editors. World Health Organization Classification of Tumours. Pathology and Genetics - Tumours of Nervous System. Lyon: IARC Press; 2000. p. 223-6.
Adegbite AB, Rozdilsky B, Varughese G. Supratentorial capillary hemangioblastoma presenting with fatal spontaneous intracerebral hemorrhage. Neurosurgery 1983;12:327-30.
Goto T, Nishi T, Kunitoku N, Yamamoto K, Kitamura I, Takeshima H, et al.
Suprasellar hemangioblastoma in a patient with von Hippel-Lindau disease confirmed by germline mutation study : Case report and review of the literature. Surg Neurol 2001;56:22-6.
Peker S, Kurtkaya-Yapicier O, Sun I, Sav A, Pamir MN. Suprasellar haemangioblastoma. Report of two cases and review of the literature. J Clin Neurosci 2005;12:85-9.
Kerr DJ, Scheithauer BW, Miller GM, Ebersold MJ, McPhee TJ. Hemangioblastoma of the optic nerve : Case report. Neurosurgery 1995;36:573-80.
Rubio A, Meyers SP, Powers JM, Nelson CN, de Papp EW. Hemangioblastoma of the optic nerve. Hum Pathol 1994;25:1249-51.
Kachhara R, Nair S, Radhakrishnan VV. Sellar-sphenoid sinus hemangioblastoma : Case report. Surg Neurol 1998;50:461-3.
Isaka T, Horibe K, Nakatani S, Maruno M, Yoshimine T. Hemangioblastoma of the third ventricle. Neurosurg Rev 1999;22:140-4.
Naik RT, Purohit AK, Dinakar I, Ratnakar KS. Hemangioblastoma of the IV ventricle. Childs Nerv Syst 1995;11:499-500.
Giannini C, Scheithauer BW, Hellbusch LC, Rasmussen AG, Fox MW, McCormick SR, et al.
Peripheral nerve hemangioblastoma. Mod Pathol 1998;11:999-1004.
Patton KT, Satcher RL Jr, Laskin WB. Capillary hemangioblastoma of soft tissue : Report of a case and review of the literature. Hum Pathol 2005;36:1135-9.
Rosenblum MK, Bilbao JM, Cyn-Ang L. Neuromuscular system. In: Rosai & Ackerman's Surgical Pathology. 9 th
ed. India: Mosby Publication, Thomson Press (India) Ltd.; 2004. p. 2587-9.
Jones RV, Ammerman JM. Intraoperative pathologic evaluation of central nervous system hemangioblastoma. Pathol Case Rev 2001;6:212-7.
Commins DL, Hinton DR. Cytologic features of hemangioblastoma : Comparison with meningioma, anaplastic astrocytoma and renal cell carcinoma. Acta Cytol 1998;42:1104-10.
Silverman JF, Dabbs DJ, Leonard JR 3rd, Harris LS. Fine needle aspiration cytology of hemangioblastoma of the spinal cord. Report of a case with immunocytochemical and ultrastructural studies. Acta Cytol 1986;30:303-8.
Ho KL. Ultrastructure of cerebellar capillary hemangioblastoma. II. Mast cells and angiogenesis. Acta Neuropathol 1984;64:308-18.
Zec N, Cera P, Towfighi J. Extramedullary hematopoiesis in cerebellar hemangioblastoma. Neurosurgery 1991;29:34-7.
Bret P, Streichenberger N, Guyotat J. Metastasis of renal carcinoma to a cerebellar hemangioblastoma in a patient with von Hippel Lindau disease : A case report. Br J Neurosurg 1999;13:413-6.
Hufnagel TJ, Kim JH, True LD, Manuelidis EE. Immunohistochemistry of capillary hemangioblastoma. Immunoperoxidase-labeled antibody staining resolves the differential diagnosis with metastatic renal cell carcinoma, but does not explain the histogenesis of the capillary hemangioblastoma. Am J Surg Pathol 1989;13:207-16.
Hoang MP, Amirkhan RH. Inhibin alpha distinguishes hemangioblastoma from clear cell renal cell carcinoma. Am J Surg Pathol 2003;27:1152-6.
Becker I, Paulus W, Roggendorf W. Histogenesis of stromal cells in cerebellar hemangioblastomas. An immunohistochemical study. Am J Pathol 1989;134:271-5.
Smalley SR, Schomberg PJ, Earle JD, Laws ER Jr, Scheithauer BW, O'Fallon JR. Radiotherapeutic considerations in the treatment of hemangioblastomas of the central nervous system. Int J Radiat Oncol Biol Phys 1990;18:1165-71.
de la Monte SM, Horowitz SA. Hemangioblastomas : Clinical and histopathological factors correlated with recurrence. Neurosurgery 1989;25:695-8.
Faiss J, Wild G, Schroth G, Heiss E, Melms A. Multiple supratentorial hemangioblastomas following primary infratentorial manifestation. Clin Neuropathol 1991;10:21-5.
Weil RJ, Vortmeyer AO, Zhuang Z, Pack SD, Theodore N, Erickson RK, et al.
Clinical and molecular analysis of disseminated hemangioblastomatosis of the central nervous system in patients without von Hippel-Lindau disease. Report of four cases. J Neurosurg 2002;96:775-87.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]